孤啡肽对大鼠顶叶皮层神经元延迟整流钾电流的抑制作用

目的研究孤啡肽(orphanin FQ/nociceptin,OFQ/N)对大鼠顶叶皮层神经元延迟整流钾电流(IK)的影响,初步探讨其干扰学习记忆过程的离子机制。方法采用全细胞膜片钳技术,观察OFQ/N对急性分离的大鼠顶叶皮层神经元IK的作用。结果①OFQ/N明显抑制IK,并呈剂量依赖性(P<0.05)。②0.1μmol.L-1OFQ/N使IK的电流-电压(I-V)曲线降低(n=8,P<0.01)。③0.1μmol.L-1OFQ/N使IK激活曲线的半数激活电压(V1/2)和斜率因子(k)分别由给药前的(-43.4±6.1)mV和(11.5±1.1)mV变为给药后的(-19.1±4.6)mV和(17.3±3.2)mV(n=8,P<0.01)。④0.1μmol.L-1OFQ/N使IK失活曲线的半数失活电压(V1/2)和斜率因子(k)分别由给药前的(-68.8±2.6)mV和(16.5±1.7)mV变为给药后的(-76.8±2.8)mV(n=5,P<0.01)和(15.7±3.1)mV(n=5,P>0.05)。结论OFQ/N可抑制大鼠顶叶皮层神经元IK,使IK激活曲线右移,失活曲线左移。

Inhibition of OFQ/N on the delayed rectifier potassium currents in acutely dissociated rat parietal cortical neurons

Aim To study effects of orphanin FQ/nociceptin (OFQ/N) on the delayed rectifier potassium current (IK) in rat parietal cortical neurons and investigate the ionic basis for the behavioral observations of OFQ/N affecting learning and memory. Methods Effects of OFQ/N on IK were investigated by using the whole-cell patch clamp technique in acutely dissociated rat parietal cortical neurons. Results IK was inhibited by OFQ/N (0.01~10 μmol·L-1) in a concentration-dependent manner. At the concentration of 0.1 μmol·L-1, amplitudes of IK decreased at different membrane potentials by OFQ/N. OFQ/N (0.1 μmol·L-1) shifted the activation curve of IK to positive potential from (-43.4±6.1) mV to (-19.1±4.6) mV (n=8, P<0.01) and changed its slope factor (k) from (11.5±1.1) mV to (17.3±3.2) mV (n=8,P<0.01). OFQ/N (0.1 μmol·L-1) caused a significant hyperpolarizing shift of the inactivation curve from (-68.8±2.6) mV to (-76.8±2.8) mV(n=5,P<0.01), but no significant effect on its K(n=5,P>0.05). Conclusion OFQ/N inhibits IK of parietal cortical neurons of rats. It suggests that behavioral effects of OFQ/N on memory and learning may be partly mediated by the inhibitory effects of OFQ/N on IK.